DESCRIPTION (adapted from the application) The Diabetes Prevention Program (DPP) is an NIH-sponsored multicenter study with the specific objective of comparing, in high risk individuals, the efficacy of three intervention methods (intensive behavior modification, metformin, and troglitazone) vs control placebo group in preventing or delaying conversion of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). A total of 4000 subjects (from 26 clinical centers) of whom 50% will consist of minority groups, will be randomly assigned to one of the four groups. Since the DPP is not designed to study the mechanism of action of these interventions, the present proposal is an ancillary study to the DPP to investigate the mechanisms by which the three interventions affect glucose intolerance and insulin resistance. Other rationales for the proposed study are that: (a) hyperandrogenism and decreased sex hormone binding globulin (SHBG) are known to be additional risk factors for development of NIDDM in certain female populations, (b) hyperandrogenism of gonadal origin [i.e. testosterone(T), and androstenedione(A)] is believed to be more deleterious to glucose tolerance and insulin sensitivity than adrenal androgens [i.e. DHEA(D) DHEAS(DS)] and c) recent preliminary studies suggest that metformin, troglitazone and exercise plus dietary modification alter androgenic profiles and improve glucose intolerance, possibly by three different mechanisms. Therefore, the DPP offers a unique opportunity to study the mechanism of action of these three interventions. We hypothesize that those modalities which most improve glucose intolerance and insulin resistance will be associated with more favorable androgenic profiles (i.e. lower T/D ratio) and CV risk factors. The specific aim of this ancillary study is to recruit 200 pre- and perimenospausal women from eight of the DPP centers (equally distributed among the four treatment groups) and among three ethnic groups (Caucasians, Hispanics and African-Americans) to: (a) assess insulin secretion by OGTT, (b) measure androgenic profiles, (c) measure body fat distribution by CT Scan, and lean body mass (LBM) and fat content by DEXA and (d) study glucose and insulin metabolism and clearance, and insulin sensitivity by the use of modified frequently sampled iv glucose tolerance test (FSIGT). These studies will be done at baseline, and at the end of the 1st and 3rd year of intervention. The proposed ancillary study should, therefore, enable us to assess the correlation between glucose intolerance, insulin resistance, and androgenic profile, as well as the effect of various treatment modalities on them and the mechanism of action, in a setting of multiethnic diabetes prevention program.